1. Field of the Invention
The present invention relates to a medical agent for preventing or treating diseases resulting from inflammation or remodeling, particularly diseases such as arteriosclerosis, heart failure, cerebrovascular disorder, and hypertensive kidney disease; and to a method for preventing or treating the diseases.
2. Description of the Related Art
In recent years, with the aging of the population and Westernized eating habits, prevalence of high blood pressure, hyperlipemia, and diabetes has increased. As a result, arteriosclerotic diseases are increasing year by year. Arteriosclerotic diseases include diseases such as stroke, an ischemic heart disease, hypertensive nephropathy, ophthalmopathy, heart failure, aortic aneurysm, arteriosclerosis obliterans, hypertensive emergency, and cerebrovascular disorder. More than half of the elderly people aged 75 or more has some sort of disease and reduced quality of life (QOL). It is known that these diseases are caused by common pathologic conditions, arteriolar and aortic damages.
Chronic injury in endothelial cells triggers the onset of arteriosclerosis. Endothelial cells line the artery, forming a layer, and play an important role such as regulation of vascular permeability, production and/or secretion of antithrombotic substances, smooth muscle cell-growth inhibition, and production of vasoactive substances. In the injured vascular endothelium, these functions are impaired. In addition, on the surface of activated or injured endothelial cells, adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are expressed. Monocyte recognizes adhesion molecules, adheres to the surface of endothelial cells, is recruited under the layer of endothelial cells, and then matures into a macrophage. The macrophage beneath endothelial cells is eventually converted into a foam cell, forming atherosclerotic plaque. Inflammatory cytokine is involved in the expression of adhesion molecules and migration of monocyte.
It is also known that in the pathologic condition such as high blood pressure that is involved in the development of arteriosclerosis, responding to various load applied on the blood vessel, the cytoarchitecture of blood vessel wall changes, causing remodeling of blood vessel. Remodeling of blood vessel refers to the change of the structure of vascular tissue as a result of the injury or abnormal proliferation of vascular tissue due to mechanical load or change of humoral factor. Originally, remodeling is a mechanism for responding to change in pathologic condition; it is known that remodeling has an adverse effect on blood vessel such as hardening of blood vessel wall and decrease of inner diameter during the process. It is known that in the remodeling of blood vessel, smooth muscle cells from medial layer in blood vessel, become hypertrophied. Growth factors such as angiotensin II and platelet derived growth factor (PDGF) are involved in this hypertrophy of smooth muscle cells.
As described above, the mechanism of onset and/or development of arteriosclerosis is complicated. Besides, many of the mechanisms are yet to be elucidated. There is a need for efficient methods for preventing and/or treating arteriosclerosis. Moreover, there is a need for efficient methods for preventing and/or treating diseases resulting from one of inflammation and remodeling including arteriosclerosis.
In recent years, attention has been paid to various bioactive effects of water that contains nanobubbles of oxygen in large amount (oxygen-nanobubble water) on living organisms. For example, oxygen-nanobubble water improves adaptability of fish and shellfish to environmental change, or restores a debilitated individual quickly. Nanobubbles are ultrafine bubbles with a nano-order diameter and are typically generated in the process where microbubbles (minute bubble with a diameter of 50 μm or less) shrink. Since nanobubbles are self-pressurized by the action of surface tension, they are completely dissolved rapidly. Thus, the lifetime was considered to be short in general. However, it is reported that in the case where nanobubbles are coated with shell by a surfactant, or in the case where they are subjected to electrostatic repulsion due to surface charging, even bubbles in nano-order can exist for a certain period. Especially, nanobubbles stabilized due to charging effect retain properties as bubble; thus various applications, such as direct action to organisms at cellular level, are expected (See, for example, Japanese Patent Application Laid-Open (JP-A) No. 2005-245817).